The objective of this program is to develop new high-speed ultrahigh resolution optical coherence tomography (OCT) technology for imaging retinal structure and to perform clinical studies of retinal disease and glaucoma. This program is an ongoing, multidisciplinary, collaborative effort between investigators at the Massachusetts Institute of Technology, New England Eye Center, and University of Pittsburgh Medical Center. The program integrates the development of new high-speed ultrahigh resolution OCT technology, which will have widespread research and clinical applications, with clinical investigations to elucidate pathogenesis and to improve diagnosis and monitoring of retinal diseases and glaucoma. OCT is analogous to ultrasound imaging except that cross-sectional images of tissue are generated by using echoes of light rather than sound. OCT enables real-time, cross-sectional imaging of retinal structure at unprecedented resolution. Our specific aims are: 1. To develop high-performance ultrahigh resolution OCT technology for imaging and quantitatively assessing retinal structure and pathology. Ultrahigh resolution OCT achieves axial image resolutions of approximately 2-3 mu/m, 5x better than conventional OCT with 10 mu/m resolution. New techniques for high speed OCT, known as spectral/Fourier domain detection, can increase imaging speeds by 50-100x. These advances will dramatically improve the ability to visualize, map, and quantify retinal pathology. 2. To develop new imaging protocols and processing methods to visualize, map, and measure retinal architecture such as the nerve fiber layer, ganglion cell layer, photoreceptors, and other intraretinal layers. To develop methods for three-dimensional retinal imaging and visualization. 3. To perform clinical studies in patients with a cross section of retinal diseases in order to investigate the ability to detect and quantify changes associated with retinal pathology and disease. 4. To investigate the reproducibility of quantitative measurements in normal and glaucoma subjects and test the feasibility for glaucoma diagnosis. 5. To quantitatively assess retinal structure in normal subjects in order to assess population variations and develop a normative baseline. The development and application of high-speed ultrahigh resolution OCT technology will enable new methods for visualization, mapping, and quantitative assessment of retinal structure and pathology. These advances promise to help elucidate disease pathogenesis, provide more sensitive and earlier diagnosis of disease, as well as more accurate monitoring of disease progression and response to therapy.